title: Vasomotor and fibrinolytic responses to kinin receptor agonists in the atherosclerotic human lower limb.
abstract: Upregulation of vascular B(1) kinin receptor expression has been reported in human atheroma, but its role remains unclear. We examined vasomotor and fibrinolytic responses to selective B(1) and B(2) kinin receptor agonism in the human femoral circulation and correlated responses with femoral arterial plaque load. Femoral arterial cross-sectional area, blood flow and plaque volume were determined using intravascular ultrasound and Doppler during selective arterial infusion of Lys-des-Arg(9)-bradykinin (B(1) agonist), bradykinin (B(2) agonist) and sodium nitroprusside in eleven patients undergoing diagnostic coronary angiography. Net release of tissue plasminogen activator was determined across the femoral vascular bed. Mean femoral arterial plaque load was 8.1 (±0.9) mm(3)/mm of vessel. Bradykinin and sodium nitroprusside caused dose-dependent increases in femoral blood flow (p < 0.05 and p < 0.005, respectively). Bradykinin caused a dose-dependent increase in net tissue plasminogen activator release (p < 0.05), which was augmented by angiotensin-converting enzyme inhibition (p < 0.05). There were no correlations between plaque load and bradykinin-mediated vasodilation or tissue plasminogen activator release. Lys-des-Arg(9)-bradykinin had no effect on blood flow or tissue plasminogen activator release. The vasomotor and fibrinolytic actions of bradykinin in the femoral circulation are mediated solely by the B(2) kinin receptor, irrespective of the presence of atheroma. In keeping with previous data, bradykinin-mediated tissue plasminogen activator release was augmented in the presence of angiotensin-converting enzyme inhibition consistent with its putative vascular protective effect.
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Room F2339, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 5SB, UK. nick.cruden@ed.ac.uk
authors.forename: Nicholas L M
authors.initials: NL
authors.lastname: Cruden
authors.forename: Ninian N
authors.initials: NN
authors.lastname: Lang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: MacGillivray
authors.forename: Neal G
authors.initials: NG
authors.lastname: Uren
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology; D001783:Blood Flow Velocity; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007609:Kallidin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D043783:Receptor, Bradykinin B1 / Q000819:agonists* / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000819:agonists* / Q000378:metabolism; D012039:Regional Blood Flow; D012606:Scotland; D010959:Tissue Plasminogen Activator / Q000097:blood; D018608:Ultrasonography, Doppler; D018084:Ultrasonography, Interventional; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D014665:Vasodilator Agents; D009599:Nitroprusside; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; D010959:Tissue Plasminogen Activator; D001920:Bradykinin